Injury to the vascular system can lead to a number of undesirable health conditions, including, for example, forms of atherosclerosis and arteriosclerosis. The contribution of the various biological pathways leading to such undesirable health conditions is not fully understood, and prophylaxis against such conditions has been less than fully effective.
A common injury to the vascular system occurs as a side effect of a medical procedure for treating ischemic heart disease. Ischemia refers to a lack of oxygen due to inadequate perfusion of blood. Ischemic heart disease is characterized by a disturbance in cardiac function due to an inadequate supply of oxygen to the heart. The most common form of this disease involves a reduction in the lumin of coronary arteries, which limits coronary blood-flow.
When ischemic heart disease becomes very serious, then management must be invasive. Until recently, ischemic heart disease was treated by coronary-artery, bypass surgery. Less invasive procedures, however, now have been developed. These procedures involve the use of catheters introduced into the narrowed region of the blood vessel ("the stenosis") for mechanically disrupting, laser ablating or dilating the stenosis.
The most widely used method to achieve revascularization of a coronary artery is percutaneous transluminal coronary angioplasty. A flexible guide wire is advanced into a coronary artery and positioned across the stenosis. A balloon catheter then is advanced over the guide wire until the balloon is positioned across the stenosis. The balloon then is repeatedly inflated until the stenosis is substantially eliminated. This procedure, as compared to heart surgery, is relatively noninvasive and can result in hospital stays of only three days. The procedure is an important tool in the management of serious heart conditions.
A serious drawback to angioplasty procedures is the re-occurrence of the stenosis at the site of the angioplasty, or "restenosis". The clinical effects of angioplasty include endothelial denudation, vascular wall damage and rupture of the tunica intima vasorum. These injuries have been found to cause in many cases proliferation of the arterial smooth muscle cells and, it is believed, restenosis. Restenosis may occur in as many as 40% of patients that have undergone an angioplasty procedure.
To date, there is no effective treatment for preventing restenosis. Although the use of drugs such as anticoagulants have been suggested, restenosis still remains the main complication of successful angioplasty procedures.
There has been some attempt to delineate the role that platelets might play in restenosis following angioplasty. Although the role of platelets has remained unclear, it is believed that: (1) platelets are involved in the initiation of smooth muscle proliferation following angioplasty; but (2) through release of platelet derived growth factor, platelets may regulate the movement of smooth muscle cells into the intima following angioplasty. These conclusions were reached based upon studies comparing the response to angioplasty of thrombocytopenic animals to normal animals. The thromobocytopenic animals were depleted of circulating platelets using anti-platelet antibodies. Even if this approach were believed to be capable of preventing restenosis, it would not be a desirable approach in humans, in that it requires depleting circulating platelets. It also might require human or humanized anti-platelet antibodies which presently are not believed to be available.